In situ forming PLGA implant for 90 days controlled release of leuprolide acetate for treatment of prostate cancer

Abstract

In prostate cancer, hormone therapy via leuprolide acetate drug (LUP) is used to lower the level of testosterone down to castration level to effectively control the development of prostate cancer. The objective of this study was to evaluate the effective parameters in degradation and controlled release of an injectable in situ formed polymeric implant, loaded with leuprolide acetate, in order to achieve an optimum formulation for sustained drug release for 90 days with minimum burst release. The main problem associating with such implants is their high burst release. Designing an injectable implant with sustained and minimum burst release has thus become an attractive challenge in drug delivery field. Effects of type of poly(lactic‐co‐glycolic acid) 75:25 copolymers (RG752, RG756) and addition of nano‐hydroxyapatite (HA) particles on degradation rates of the implants and release profiles were examined in vitro and in vivo in a rabbit animal model. Results showed that implants containing polymers with higher molecular weights had significantly lower weight loss and molecular weight reduction. Adding nanoparticles of hydroxyapatite into poly(lactic‐co‐glycolic acid) implants caused further reduction in degradation rates, leading to a more sustained drug release in vivo, with reduced burst release. Different conventional kinetic models were applied to drug release and degradation data. The degradation data fit well to the first‐order degradation model. Higuchi model was the best kinetic release model fitted to the experimental in vitro release data. This study led to an optimum formulation (RG756:RG752 3:1 + 5% HA) with sustained leuprolide release and testosterone suppression over a 90‐day period with significant decrease of burst release phase (50%, p < 0.001) compared with the conventional Eligard formulation. The histopathology test showed that the formulated implant had no effects of toxicity or tissue necrosis in organs of the animal model. Copyright © 2017 John Wiley & Sons, Ltd.

Modelling of combination therapy using implantable anticancer drug delivery with thermal ablation in solid tumor

“…The implant releases the anticancer drug over two phases, namely, burst and sustained releases. For example, in-situ forming implants (ISFIs) have a dual-release pattern with a large undesirable burst release, which may cause major toxicity problems and consume the loaded drug in the implants rapidly 10 . Designing this type of implants with a minimum initial burst release becomes an attractive challenge, and one of the key issues in the design of ISFIs 11 .…”

Three-Dimensional Culture System of Cancer Cells Combined with Biomaterials for Drug Screening

“…As an example, leuprolide-loaded PLGA microparticles are used for the treatment of breast or prostate cancer. The microparticles realize an extended release of leuprorelin, which enables once every few months [ 179 ]. The basic properties of PLGA are usually given by molecular weight and the LA/GA ratio.…”

Biomaterial-Assisted Regenerative Medicine

“…Due to its biodegradability, biocompatibility, or ease of handle, PLGA is widely used in medical fields. For example, PLGA microparticles containing leuprolide are used to treat breast or prostate cancer [164]. PLGA is often selected for tissue engineering, especially for the brain or neuron [165].…”